BACKGROUND: Acute cerebral infarction (ACI) is a common cerebrovascular disease in clinical practice. OBJECTIVE: The present study aims to investigate the efficacy and safety of alteplase and urokinase in treating ACI. METHODS: A total of 96 patients with ACI, who were treated with alteplase and urokinase, were selected as the main subjects. Among these patients, 45 patients with ultra-early acute cerebral infarction, who received intravenous thrombolysis with RT-PA (alteplase), were included in the treatment group, while 51 patients with acute cerebral infarction, who were treated with urokinase in the same time period, were included in the control group. RESULTS: The National Institute of Health Stroke Scale (NIHSS) scores were significantly lower in the treatment group and control group (P< 0.05) at two hours, seven days and 14 days after thrombolysis, when compared to those before thrombolysis. The bleeding rate was significantly lower in the control group, when compared to the treatment group (P< 0.05). CONCLUSION: The intravenous thrombolysis with urokinase or alteplase in the ultra-early stage of acute cerebral infarction can reduce the neurological injury symptoms and effectively improve the prognosis of patients with stroke. Urokinase is lower in risk of bleeding, but better in safety, when compared to alteplase.